Measurement of internal body time by blood metabolomics

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 24; pp. 9890 - 9895
• Main Authors: Minami, Yoichi, Kasukawa, Takeya, Kakazu, Yuji, Iigo, Masayuki, Sugimoto, Masahiro, Ikeda, Satsuki, Yasui, Akira, van der Horst, Gijsbertus T.J, Soga, Tomoyoshi, Ueda, Hiroki R
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.06.2009; National Acad Sciences
• Subjects: Animals; Biological Clocks; Biological Sciences; Bleeding time; Blood; Blood - metabolism; Blood plasma; Chromatography, Liquid; Chronobiology disorders; Circadian Rhythm; Female; Jet Lag Syndrome - blood; Jet Lag Syndrome - physiopathology; Male; Mass Spectrometry; Mass spectroscopy; Measurement; Medical genetics; Metabolic disorders; Metabolites; Metabolomics; Mice; Mice, Inbred CBA; Plasma; Rodents; Toxicity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0900617106

Detection of internal body time (BT) via a few-time-point assay has been a longstanding challenge in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To address this challenge, we previously developed the concept, "molecular-timetable method," which was originally inspired by Linné's flower clock. In Linné's flower clock, one can estimate the time of the day by watching the opening and closing pattern of various flowers. Similarly, in the molecular-timetable method, one can measure the BT of the day by profiling the up and down patterns of substances in the molecular timetable. To make this method clinically feasible, we now performed blood metabolome analysis and here report the successful quantification of hundreds of clock-controlled metabolites in mouse plasma. Based on circadian blood metabolomics, we can detect individual BT under various conditions, demonstrating its robustness against genetic background, sex, age, and feeding differences. The power of this method is also demonstrated by the sensitive and accurate detection of circadian rhythm disorder in jet-lagged mice. These results suggest the potential for metabolomics-based detection of BT ("metabolite-timetable method"), which will lead to the realization of chronotherapy and personalized medicine.